Summary of work: We have studied the role of the aging gene, p21 on the DNA repair process. Two components of the p21 protein were purified, the C- and B terminals. Both p21 and its C-terminal region inhibit DNA repair synthesis activity using in vitro cell extracts, while the N-terminal region does not. The addition of p21 antibodies alleviates this inhibition, indicating the effect is specific to p21. Addition of excess PCNA also alleviates this inhibition, suggesting that the inhibition of repair activity by p21 (and its C-terminal fragment) is mediated through its interaction with PCNA. This inhibitory effect of p21 on the DNA repair process is also demonstrated in vivo in intact cells by the electroporetion of the p21 protein. The SCID mouse is severely immunodeficient and it has been shown to be deficient in the repair of DNA double strand breaks. We demonstrate that fibroblasts from this mouse is also deficient in a component of nucleotide excision repair, transcription coupled DNA repair. The role of this form of DNA repair in immunodeficiency is being explored.